Seremet Teofila, Lienard Danielle, Suppa Mariano, Trepant Anne-Laure, Rorive Sandrine, Woff Erwin, Cuylits Nicolas, Jansen Yanina, Schreuer Max, Del Marmol Véronique, Neyns Bart
aDepartment of Medical Oncology, University Hospital Brussels Departments of bDermatology cPathology dNuclear Medicine, Erasme Hospital, Brussels, Belgium.
Melanoma Res. 2015 Apr;25(2):180-3. doi: 10.1097/CMR.0000000000000145.
The treatment of locally advanced metastasized melanoma is challenging because there is no level 1 evidence to guide clinical decision-making. Moreover, the treatment options available fail to improve overall survival and are associated with considerable morbidity. Here, we show that systemic treatment with BRAF inhibitor vemurafenib substituted by dual BRAF/MEK inhibition (dabrafenib and trametinib) before surgery can offer the potential to cure the initially difficult or inoperable melanoma. A 62-year-old woman was diagnosed with an AJCC stage IIIB melanoma harboring the BRAF V600E mutation after a complete initial evaluation. Clinically, the patient presented a large primary lesion that was surrounded by ∼25 secondary epidermotropic lesions both satellite and 'in transit' with a diameter between 1 and 6 mm. Following multidisciplinary consultation, the patient was started on 960 mg twice-daily vemurafenib, which was stopped and resumed at 720 mg twice daily, and finally substituted with the combination dabrafenib and trametinib to reduce the persistent side effects. Successive clinical examinations had shown a progressive reduction in the thickness of the melanoma lesions. After about 5 months of therapy, surgery was performed and the histopathological analysis showed an almost complete regression of tumor cells. The treatment with dabrafenib/trametinib was continued only 3 months after surgery and stopped at the patient's request. The patient currently remains in complete remission at 8 months after surgery. The case presented here supports the use of neoadjuvant treatment with BRAF inhibitors in advanced 'in transit' melanoma.
局部晚期转移性黑色素瘤的治疗具有挑战性，因为没有一级证据来指导临床决策。此外，现有的治疗方案未能提高总生存率，且伴有相当高的发病率。在此，我们表明，在手术前用BRAF抑制剂维莫非尼进行全身治疗，随后换用BRAF/MEK双重抑制（达拉非尼和曲美替尼），有可能治愈最初难以治疗或无法手术的黑色素瘤。一名62岁女性在完成初始全面评估后，被诊断为患有BRAF V600E突变的AJCC IIIB期黑色素瘤。临床上，患者有一个大的原发性病灶，周围有大约25个继发性表皮转移性病灶，包括卫星灶和“移行”灶，直径在1至6毫米之间。经过多学科会诊后，患者开始服用维莫非尼，剂量为每日两次，每次960毫克，之后停药并以每日两次，每次720毫克的剂量恢复用药，最终换用达拉非尼和曲美替尼联合用药以减轻持续的副作用。连续的临床检查显示黑色素瘤病灶厚度逐渐减小。经过约5个月的治疗后进行了手术，组织病理学分析显示肿瘤细胞几乎完全消退。达拉非尼/曲美替尼治疗仅在术后持续了3个月，并应患者要求停药。患者目前在术后8个月仍处于完全缓解状态。此处介绍的病例支持在晚期“移行”黑色素瘤中使用BRAF抑制剂进行新辅助治疗。
